Investigation of piperazine benzamides as human ß3 adrenergic receptor agonists for the treatment of overactive bladder.

The synthesis of a novel class of piperazine benzamide (reverse amides) targeting the human ß3-adrenergic receptor for the treatment of overactive bladder (OAB) is described. The SAR studies directed towards maintaining well established ß3 potency and selectivities while improving the overall pharmacokinetic profile in the reverse amide class will be evaluated. The results and consequences associated with functional activity at the norepinephrine transporter (NET) will also be discussed.

Discovery of benzamides as potent human ß3 adrenergic receptor agonists.

The paper will describe the synthesis and SAR studies that led to the discovery of benzamide (reverse amide) as potent and selective human ß3-adrenergic receptor agonist. Based on conformationally restricted pyrrolidine scaffold we discovered earlier, pyrrolidine benzoic acid intermediate 22 was synthesized. From library synthesis and further optimization efforts, several structurally diverse reverse amides such as 24c and 24i were found to have excellent human ß3-adrenergic potency and good selectivity over the ß1 and ß2 receptors. In addition to human ß1, ß2, ß3 and hERG data, PK of selected compounds will be described.

Discovery and development of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists for the treatment of diabetes.

A novel series of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists are described. The series was designed to address the suboptimal PK (pharmacokinetic) and off-target profile of a class of N-aryl-benzo-[1,4]-oxazepine-4-carboxamides, represented by 1, that were identified from a high-throughput screen of the Merck compound collection for GPR142 agonists. This work led to the discovery of 3-phenoxy-benzo-[1,2,4]-triazolo-[1,4]-oxazepine 47, a potent GPR142 agonist with an off-target and PK profile suitable for in vivo studies. This compound and a related analogue 40 were shown to be active in mouse oral glucose tolerance tests (OGTTs). Furthermore, a GPR142 knock-out mouse OGTT study with compound 40 provides evidence that its glucose-lowering effect is mediated by GPR142.

Impact of guideline directed medical therapy on myocardial function in adults with congenital heart disease.

BACKGROUND: Guideline-directed heart failure therapy with angiotensin receptor blocker/neprilysin inhibitor (ARNi) and sodium-glucose transporter inhibitors (SGLT2i) has been incrementally beneficial in improving outcomes in heart failure patients. OBJECTIVE: Evaluate the feasibility and efficacy of guideline-directed medical therapy (GDMT) in adults congenital heart disease (ACHD) patients. METHODS: In a retrospective cohort study, ACHD patients with either New York Heart Association (NYHA) Class II symptoms or systemic ejection fraction (EF) <45%, optimized on a combination of beta-blocker (BB), ARNi, mineralocorticoid receptor antagonist (MRA) and SGLT2i were evaluated. RESULTS: Forty-six patients with a mean age 42.6 ± 12.1 years prescribed GDMT were identified. Twenty-eight (61%) were male, 20 (43%) had a systemic right ventricle (RV) and 9 (20%) had single-ventricle physiology. Over the optimization period, 20 (43%) were sustained on ARNi and 42 (91%) on SGLT2i in addition to treatment with BB and MRA. Over a period of 45 weeks, echocardiography parameters for left ventricle (LV) ejection fraction (EF) (+7.5%, p = 0.006), systemic ventricle (SV) velocity time integral (VTI) (+1.9 cm, p = 0.012) and LV global longitudinal strain (GLS) (-2.5%, p = 0.005) improved when 3-4 medications were used versus 1-2 medications alone. The use of either ARNi or SGLT2i (+8.1%, p = 0.017) or in combination (+7.0%, p = 0.043) increased LVEF compared to the use of neither medication. CONCLUSION: Combination GDMT is beneficial in improving myocardial characteristics in ACHD patients with systemic RV and LV.

Inclusion of men in health services and educational activities: the fathers' perceptions.

OBJECTIVE: To learn about the perception of fathers regarding their inclusion in health services and/or educational activities. METHOD: Qualitative, exploratory, and descriptive study addressing 22 fathers participating in a group of pregnant women in Rio Grande, RS, Brazil. Data were collected through semi-structured interviews and analyzed using the content analysis technique. RESULTS: The following categories emerged from the participants' reports: fathers' perceptions regarding their presence in health services and fathers' perceptions regarding their participation in the group of pregnant women. Additionally, they provided contributions and suggestions regarding their experiences with the group's meetings. CONCLUSION: The participants felt excluded from the services, which shows that health intervention strategies need to be (re)constructed to implement actions that include fathers as active participants in care, so they recognize the importance of their role in healthy human development.

Cancer Patient Experience in a Nuclear Medicine Department: Comparison Between Bone Scintigraphy and 18F-FDG PET/CT.

Our objective was to assess the anxiety level in cancer patients undergoing nuclear medicine exams and to identify how professionals can improve patient experience. Methods: In total, 94 patients undergoing 99mTc-hydroxymethylene diphosphonate (99mTc-HDP) bone scintigraphy (BS) or 18F-FDG PET/CT completed 2 scan-experience questionnaires and the Spielberger State Anxiety Inventory (STAI-S) before the scan and after image acquisition. Results: Before the exam, the mean anxiety levels were higher for the 99mTc-HDP BS group than for the 18F-FDG PET/CT group. After the exam, the opposite was true. Both groups experienced a reduction in anxiety after the scan (prescan score, 51.75 for 99mTc-HDP BS and 44.67 for 18F-FDG PET/CT; postscan score, 36.70 for 99mTc-HDP BS and 38.82 for 18F-FDG PET/CT). The greatest anxiety factor for the 99mTc-HDP BS group was the duration of the exam (mean ± SD, 5.34 ± 2.08), whereas for the 18F-FDG PET/CT group it was the result (5.40 ± 1.80). Conclusion: Patients undergoing nuclear medicine exams in an oncologic context had significant anxiety levels before and after their scans. However, 99mTc-HDP BS and 18F-FDG PET/CT had different triggers. It is of extreme importance that health-care professionals be aware of these peculiarities and adjust their procedures accordingly.

Prevalence and associated prenatal and perinatal risk factors for oropharyngeal dysphagia in high-risk neonates in a South African hospital.

BACKGROUND: The prevalence of neonatal oropharyngeal dysphagia (OPD) in high-risk infants in lower-middle-income countries is unknown. OBJECTIVES: To determine the prevalence and associated risks for OPD in high-risk neonates in order to allow timely intervention for OPD, minimising negative outcomes. METHOD: A prospective cross-sectional observational study was conducted in an urban hospital in South Africa. Clinical feeding assessments were conducted using the Neonatal Feeding Assessment Scale with all available neonates in neonatal care. RESULTS: The sample of 81 high-risk neonates (mean chronological age = 11.7 days; standard deviation = 15.6 days) had been feeding orally for 2 days and were approaching discharge. Fifty-two participants (64.2%) had OPD. Risks likely associated with OPD included breech presentation, septicaemia and other infections, spending more than 1 day on a warm table or incubator, neurological conditions, prenatal exposure to maternal smoking, siblings with mental or neurological disability, participants with congenital disorders, preterm birth ( 37 weeks), low birth weight ( 2500 g), or retinopathy of prematurity. CONCLUSION: An unexpected high prevalence of OPD was found in neonates already deemed ready for oral feeding and approaching discharge. Timely early involvement of the Speech-Language Therapists (SLTs) in decision-making about feeding readiness may prevent serious complications of neonatal OPD. Findings may inform South African neonatal clinicians. The study provides motivation for early intervention from SLTs before the infant and mother are discharged from high care and dispersed to communities where intervention services may be scarce.

Inclusion of men in health services and educational activities: the fathers' perceptions / Inclusión de los hombres en servicios de salud y actividades educativas: percepción de los padres / Inclusão de homens em serviços de saúde e atividades educativas: percepção dos pais

ABSTRACT Objective: To learn about the perception of fathers regarding their inclusion in health services and/or educational activities. Method: Qualitative, exploratory, and descriptive study addressing 22 fathers participating in a group of pregnant women in Rio Grande, RS, Brazil. Data were collected through semi-structured interviews and analyzed using the content analysis technique. Results: The following categories emerged from the participants' reports: fathers' perceptions regarding their presence in health services and fathers' perceptions regarding their participation in the group of pregnant women. Additionally, they provided contributions and suggestions regarding their experiences with the group's meetings. Conclusion: The participants felt excluded from the services, which shows that health intervention strategies need to be (re)constructed to implement actions that include fathers as active participants in care, so they recognize the importance of their role in healthy human development.

RESUMEN Objetivo: Conocer la percepción del padre sobre su inclusión en los servicios de salud y/o actividades educativas. Método: Estudio cualitativo, exploratorio y descriptivo, realizado con 22 padres participantes de un grupo de gestantes, en la ciudad de Rio Grande/RS. Los datos fueron recolectados a través de entrevistas semiestructuradas y analizados mediante la técnica de análisis de contenido. Resultados: De los discursos de los participantes surgieron las siguientes categorías: percepción de los padres sobre su presencia en los servicios de salud; percepción de los padres sobre su participación en el grupo de gestantes y aportes y sugerencias a través de sus experiencias en la participación en los encuentros. Conclusión: Los participantes se sintieron excluidos de los servicios, lo que demuestra que las estrategias de intervención en salud necesitan ser (re)construidas, con el objetivo de implementar acciones que incluyan al padre como participante activo en el cuidado, reconociendo su relevancia para el desarrollo humano saludable.

RESUMO Objetivo: Conhecer a percepção dos pais sobre a sua inclusão nos serviços de saúde e/ou em atividades educativas. Método: Estudo qualitativo, exploratório e descritivo, realizado com 22 pais participantes de um grupo de gestantes, no município do Rio Grande/RS. Os dados foram coletados através de entrevista semiestruturada e analisados pela técnica da análise de conteúdo. Resultados: A partir dos discursos dos participantes emergiram as categorias: percepção dos pais sobre sua inserção nos serviços de saúde; percepção dos pais frente sua participação no grupo de gestantes. Conclusão: Participantes sentiram-se excluídos dos serviços, demonstrando que estratégias de intervenção em saúde precisam ser (re)construídas, visando implementar ações que insiram os pais como participantes ativos no cuidado, reconhecendo sua relevância para o desenvolvimento humano saudável.

Alterações no papanicolau: dificuldades no seguimento das orientações profissionais / Changes in pap: difficulties in following professional guidance

O objetivo deste estudo é conhecer as dificuldades enfrentadas pelas mulheres que apresentaram algum tipo de alteração no exame Papanicolau, para seguir as orientações indicadas pelos profissionais de saúde. Trata-se de um estudo exploratório qualitativo realizado na cidade do Rio Grande - RS. Os sujeitos foram 52 mulheres que apresentaram alterações no Exame Papanicolau realizado pelo Sistema Único de Saúde, durante o ano de 2010 e o primeiro semestre de 2011. Os resultados foram divididos em três categorias: elementos facilitadores do seguimento das orientações; elementos dificultadores do seguimento das orientações e dificuldades referentes ao desconhecimento da necessidade de acompanhamento contínuo. Conclui-se que as dificuldades elencadas pelas mulheres foram em relação ao agendamento da consulta de retorno, dos exames e de cirurgia e ao número insuficiente de profissionais. Percebeu-se a importância do acolhimento da mulher pelos profissionais de saúde, com orientações claras e objetivas.

The aim of this study is to understand the difficulties faced by women who had some kind of change in Pap smears, in following the guidelines set by health professionals. This was a qualitative exploratory study conducted in the city of Rio Grande, RS. The subjects were 52 women who had an abnormal Pap Examination, conducted by the National Health System, during the year 2010 and the first half of 2011 The results were divided into three categories: enablers of following the guidelines; impediments to following the guidelines; and difficulties related to the lack of awareness of the need for continuous monitoring. Conclusion: The difficulties listed by women were related to the scheduling of return visits, examinations and surgery, and the insufficient number of professionals. The importance of inclusive care for women by healthcare professionals with clear and objective guidelines is observed.